Nilotinib is 4-Methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-N-[5-(4-(4-methyl-1H-imidazol-)-3-(trifluoromethyl)phenyl]benzamide. A particularly useful salt of nilotinib is nilotinib hydrochloride monohydrate. These therapeutic compounds have utility as inhibitors of the protein tyrosine kinase (TK) activity of Bcr-Abl. Examples of conditions that may be treated by such therapeutic compounds include, but are not limited to, chronic myeloid leukemia and gastrointestinal stromal tumors.
There is a need to formulate nilotinib and the other therapeutic compounds hereinafter disclosed into pharmaceutical compositions, especially solid oral dosage forms, such that the therapeutic benefits of the compounds may be delivered to a patient in need thereof. One problem to providing such compositions including nilotinib is the physiochemical properties of nilotinib, since nilotinib and its salts are poorly water soluble compounds and are difficult to formulate and deliver (i.e., made bioavailable when ingested orally). It is also difficult to achieve matching pharmacokinetic profiles with different dosage forms, i.e. tablets versus capsules. Another problem is a food effect, as food increases the bioavailability of nilotinib. Compared to a fasted state, nilotinib systemic exposure, as reflected by AUC and Cmax, increases markedly when the unit dosage is given shortly after food is ingested, leading to potential adverse effects in patients.